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BSG liver section and basl symposium: ‘hepatic encephalopathy‘
CXCR3 axis in patients with primary biliary cirrhosis: a novel mechanism of action of ursodeoxycholic acid
  1. P Manoussou1,
  2. M Koulentaki2,
  3. A Voumvouraki2,
  4. I Drygiannakis3,
  5. H A Papadaki,
  6. G Notas1,
  7. G Kolios1,
  8. E Kouroumalis *1,2
  1. 1Liver Research Laboratory, Faculty of Medicine, University of Crete, Greece
  2. 2Department of Gastroenterology, University Hospital of Heraklion, Crete, Greece
  3. 3Hematology Research Laboratory, Faculty of Medicine, University of Crete, Greece


Introduction Background and Aim: The CXC chemokines, MIG, IP-10 and I-TAC, are known to attract CXCR3+ T lymphocytes. CXCR3 gene generates two distinct mRNAs, CXCR3A and CXCR3B, by alternative splicing. In Primary Biliary Cirrhosis (PBC), intrahepatic bile ductules are destroyed by T lymphocytes. We investigated therefore the CXC chemokine axis in this disease.

Methods Mig, IP-10 and I-TAC mRNAs expression was studied by RT-PCR in 20 liver biopsies from PBC patients (Ludwig stage II/III) and compared with normal biopsies (NCs = 20). Serum chemokines were assessed by ELISA in 44 PBC patients (Ludwig stage II/III) and 20 normals. Measurements were repeated six months after Ursodeoxycholate (UDCA) treatment. CXCR3A and CXCR3B mRNAs expression were examined in immunomagnetically sorted CD3+ peripheral blood lymphocytes (PBL) by RT-PCR, pre and post treatment. Flow cytometry evaluated the expression of CXCR3+ in PBL of NC and patients.

Results A marked mRNA expression of MIG and IP10, but not of I-TAC, was found in PBC patients. Serum MIG (72.86 pg/ml) and IP-10 (660.1 pg/ml) were significantly increased in PBC, compared to NC (33.47 pg/ml and 37.58 pg/ml, respectively). There was a significant reduction of these proteins after treatment with UDCA (40.95 pg/ml for MIG and 289.2 pg/ml for IP-10). I-TAC was not different between groups. CXCR3A mRNA expression was found in PBLs from PBC patients and NCs. CXCR3B mRNA was expressed in 4/20 (19%) NCs and 20/20 PBC patients. Flow cytometry revealed a significantly lower CXCR3 expression in NCs (13.5%) than in PBC (37.2%) which was reduced (28.1%, p < 0.01) after UDCA administration.

Conclusion These data suggest a possible role of CXCR3-binding chemokines and their receptor in the aetiopathogenetic recruitment of lymphocytes in PBC and a new mechanism of action of UDCA.

  • CXCR3
  • primary biliary cirrhosis

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  • Competing interests None.

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